Synthetic peptides representing sequence 39 to 59 of rat Vβ8 TCR fail to elicit regulatory T cells reactive with Vβ8 TCR on rat encephalitogenic T cells

Abstract

Subpathogenic doses of syngeneic autoreactive T cells protect experimental animals against associated autoimmune disease. Preferential use of the TCR of encephalitogenic T cells suggests that this molecule serves as the target for immunoregulation in experimental autoimmune encephalomyelitis (EAE). Whether peptides derived from the Vβ8 of the rat TCR elicit regulatory T cells and produce the same vaccinating effect against EAE as do whole T cells remains unknown. Here we show that immunization of Lewis rats with Vβ8(39–59), a peptide representing residues 39 to 59 of the rat Vβ8 TCR, does not induce the production of regulatory T cells reactive to the intact TCR Vβ8 containing this sequence. Moreover, animals that had recovered from both actively induced EAE and transferred EAE did not generate regulatory T cells that recognized the Vβ8(39–59) peptide. Further, transfusion of large doses of peptide-specific T cells did not protect the animals from EAE. Our results suggest that the Vβ8(39–59) peptide may comprise so-called cryptic epitopes, which function as immunogens only when dissociated from large protein complexes.